Characteristics of bronchoalveolar lavage fluid in patients with sulfur mustard gas-induced asthma or chronic bronchitis.

PURPOSE: To examine the pattern of immunoglobulins and cellular constituents in bronchoalveolar lavage fluid obtained from patients with sulfur mustard gas-induced asthma or chronic bronchitis as compared with healthy control subjects. SUBJECTS AND METHODS: We studied two groups of nonsmoking veterans with either bronchial asthma (n = 21) or chronic bronchitis (n = 28) believed to have been caused by sulfur mustard gas exposure and a third group of healthy, nonsmoking, non-sulfur mustard gas exposed controls (n = 17). Bronchoalveolar lavage was performed in all three groups. The cellular constituents, albumin content, and immunoglobulin concentrations were determined. RESULTS: The three groups did not differ in age or in the serum albumin and immunoglobulin concentrations. The volume of bronchoalveolar lavage fluid recovered was approximately 10% less in the patients with asthma and chronic bronchitis (P = 0.008). The proportions of lymphocytes among the bronchoalveolar lavage cells were similar in all three groups, whereas the proportion of eosinophils was greater in lavage fluid from the asthmatic subjects than in either the healthy control subjects or the patients with chronic bronchitis (P = 0.0001). Both the total number of the recovered cells per milliliter of lavage fluid and the proportion of neutrophils were significantly greater in bronchoalveolar lavage from patients with chronic bronchitis than in healthy subjects or in the patients with asthma (all P <0.001). CONCLUSION: The bronchoalveolar lavage cellular constituents of patients with sulfur mustard gas-induced asthma and chronic bronchitis are similar to those that have been observed previously in patients with asthma and chronic bronchitis from other common causes.     

The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage

Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters

In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)     

Local immunity in patients with chronic bronchitis and the effects of a bacterial extract, Broncho-Vaxom, on T lymphocytes, macrophages, gamma-interferon and secretory immunoglobulin A in bronchoalveolar lavage fluid and other variables

In 28 adult patients with nonobstructive chronic bronchitis we investigated components of the immune system of the lower airways and the effects of treatment with Broncho-Vaxom (BV). An analysis of the washing from bronchoalveolar lavage (BAL) showed, in comparison with healthy controls, an elevation of total cell count (p = 0.003) as well as the IgA/albumin values (p = 0.02) and a reduction of the macrophage activity (p less than 0.001) in patients with chronic bronchitis. After BV a reduction in the total cell count (p = 0.05), an increase in the helper/suppressor T lymphocyte ratio (due mainly to the reduction in the suppressor cells; p = 0.04), a modulation of the IgA/albumin ratio, a stimulation of the impaired alveolar macrophage activity (p = 0.03) and increased concentrations of gamma-interferon (p = 0.03) were found in the BAL fluid of patients with chronic bronchitis. The salivary IgA/albumin ratio remained unchanged, the serum IgE concentration fell (p = 0.02) and the urinary IgA concentration rose (p = 0.002). Bronchial mucosa lesions, evaluated endoscopically in terms of structural damage, hyperemia and mucus production, were improved (p less than 0.01). These findings indicate that orally administered BV modulates disordered local and systemic immune functions in patients with chronic bronchitis.     

曹梦园)高迁移率族蛋白B1在香烟暴露大鼠模型中的表达

目的 探讨高迁移率族蛋白B1(HMGB1)在香烟诱导的慢性支气管炎大鼠模型中的表达及作用.方法 雄性SD大鼠随机分为正常对照组、吸烟模型组,每组14只.采用烟熏法建立慢性支气管炎大鼠模型.光镜下观察支气管肺组织病理形态学改变,分析支气管肺泡灌洗液(BALF)细胞计数和分类,用ELISA 法检测大鼠血清中HMGB1的浓度,免疫组化法检测HMGB1在肺组织的表达.结果 模型组大鼠肺组织的病理形态改变与人类慢性支气管的特点相一致.BALF中模型组细胞总数、单核巨噬细胞及中性粒细胞百分比与健康对照组比较,差异有显著性(P<0.05).与对照组相比,模型组大鼠血清HMGB1的含量显著升高(P<0.05).免疫组化染色可见HMGB1主要分布于支气管及肺泡上皮细胞,与对照组比较,模型组大鼠肺组织HMGB1的表达强度明显增强(P<0.05).结论 吸烟是慢性支气管炎的一个重要危险因素,HMGB1可能在慢性支气管炎的发病中起到一定的作用.     

Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation.

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased vascular endothelial growth factor and receptors: relationship to angiogenesis in asthma

RATIONALE: Increased vascularity is a feature of airway remodeling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Although various growth factors have been implicated in modulating vascularity, the important contributors in vivo are still being elucidated. The most likely candidate is vascular endothelial growth factor (VEGF). OBJECTIVES: We have examined VEGF and its receptors, VEGFR1 and VEGFR2, and angiopoietin-1 (Ang1) in the airways of subjects with asthma and contrasted these results with findings in normal control subjects. We aimed to explore whether these powerful angiogenic factors were expressed at elevated levels in asthmatic airways. METHODS: We obtained biopsy and bronchoalveolar lavage samples from 35 subjects with mild to moderate asthma and from 22 normal control subjects. MEASUREMENTS: We performed immunohistochemistry and image analysis to obtain quantitative measures of VEGF, VEGFR1, VEGFR2, and Ang1 staining in airway biopsies, and ELISA to assess VEGF concentration in the bronchoalveolar lavage fluid. RESULTS: VEGF staining and VEGF levels in bronchoalveolar lavage fluid were elevated in the airways of subjects with asthma and were related to the number of vessels; Ang1 staining was similarly increased. VEGFR1 was slightly higher in subjects with asthma and the VEGFR1:VEGFR2 ratio was significantly higher in subjects with asthma. We observed angiogenic sprouts (i.e., early-forming vascular structures) that were increased in number in subjects with asthma. CONCLUSIONS: Our findings suggest that VEGF, its receptors, and Ang1 are likely to be important in vascular changes in the airways of patients with asthma. Further, there are observable structures in the vessel walls of asthmatic airways that could present ongoing evidence of increased angiogenic activity.     

Neutrophilia in bronchoalveolar lavage fluid of diffuse panbronchiolitis

The clinical and pathologic features of diffuse panbronchiolitis (DPB) have been well reported to date, although its pathogenesis remains unknown. In the present study, we performed bronchoalveolar lavage (BAL) on three patients with biopsy specimen-proven DPB and eight patients with highly probable DPB (six women and five men; one smoker and ten nonsmokers), nine patients with chronic bronchitis (all men, five smokers and four nonsmokers), and nine normal control subjects (six women and three men, all nonsmokers) to clarify the cell populations in the lower respiratory tract. Neutrophils comprised 55.3 +/- 24.4 percent of recovered cells by BAL in DPB patients but only 6.6 +/- 6.4 percent in chronic bronchitis patients, and 1.8 +/- 1.5 percent in normal control subjects (p less than 0.001, all comparisons). The DPB patients also exhibited a decreased percentage of alveolar macrophages (34.9 +/- 23.5 percent) compared with chronic bronchitis patients and normal control subjects (p less than 0.001, all comparisons). The percentage of lymphocytes of the recovered lavage cells in DPB patients did not differ from that in chronic bronchitis patients and normal control subjects. These results indicate that neutrophils play an important role in the pathogenesis of DPB. They also suggest that neutrophilia of BAL-recovered fluid is a common finding in diseases associated with bronchiolar inflammation despite some clinical and pathophysiologic differences.     

Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics.

CC-chemokines are chemotactic factors expressed in a wide range of cell types and tissues. The aim of this study was to evaluate the involvement of CC-chemokines in the airways inflammation of patients affected by chronic bronchitis. The study evaluated, with an immunoassay, the concentrations of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta), in the bronchoalveolar lavage fluid (BALF) of 12 smokers affected by chronic bronchitis and 14 smoking, 15 nonsmoking and six exsmoking healthy subjects. MCP-1 was significantly increased in patients with chronic bronchitis ((mean+/-SD) 10.75+/-4.04 pg x mL(-1)) and in the smoker control group (12.39+/-5.87 pg x mL(-1)) compared with healthy exsmokers: (7.12+/-1.60 pg x mL(-1), p=0.035 and p=0.045, respectively) and nonsmokers (6.41+/-3.87 pg x mL(-1), p=0.003 and p=0.006, respectively). MIP-1alpha concentrations were undetectable. A significant difference was observed in MIP-1-beta levels in BALF of chronic bronchitics (8.11+/-5.97 pg x mL(-1)) compared to smoker (3.57+/-2.90 pg x mL(-1), p=0.018), exsmoker (3.43+/-0.68 pg x mL(-1), p=0.025) and nonsmoker (3.39+/-3.73 pg x mL(-1), p=0.008) control groups. A negative correlation was observed between MIP-1beta levels and forced expiratory volume in one second values (p=-0.64, p=0.035) in chronic bronchitics. An increase of monocyte chemotactic protein-1 is related to smoking habit and seems consistent with a lung inflammatory reaction. On the contrary, an increase in macrophage inflammatory protein-1beta levels is restricted to smokers developing chronic obstructive pulmonary disease. These data suggest a role of CC-chemokines in the pathogenesis of chronic bronchitis.     

Peripheral airway findings in chronic obstructive pulmonary disease using an ultrathin bronchoscope.

The authors performed bronchoscopic examination using an ultrathin bronchoscope to determine the characteristics of the peripheral airways in chronic obstructive pulmonary disease (COPD). The study population comprised 13 healthy control subjects, 10 patients with chronic bronchitis without airflow limitation, and 20 patients with COPD. The COPD patients were divided clinically into 10 with chronic bronchitis and 10 with pulmonary emphysema. The peripheral airways were examined using an ultrathin bronchoscope. In chronic bronchitis, peripheral airways of the 11th or 12th generation showed a high frequency of obstruction and mucosal changes such as granulation. In pulmonary emphysema, the peripheral airways frequently showed a net-like appearance of the bronchial epithelium and obstruction at the 11th or 12th generation. Morphological changes of the small airways in chronic obstructive pulmonary disease can be detected by an ultrathin bronchoscope, and this method is likely to be useful for investigating the small airways in vivo.     

Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers

The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.     

Chronic inflammation is associated with an increased proportion of goblet cells recovered by bronchial lavage

To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes.     

Clinical aspects of peripheral airway diseases in chronic obstructive pulmonary disease

We studied the site of obstructive impairment in chronic obstructive pulmonary disease (COPD). In chronic bronchitis peripheral airway inflammation caused obstructive impairment. Bronchial sensitivity increased in peripheral airways in chronic bronchitis. In bronchial asthmatics both allergic and increased bronchial sensitivity were observed in peripheral airways. The mucus occupying rat was higher in peripheral airways than central airways. Despite primary inflammation in peripheral airways in COPD, aerosolized bronchodilator dilated peripheral airway in cases of moderate asthenic.     

Time course of cigarette smoke-induced pulmonary inflammation in mice.

Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations. Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e. neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks. Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure. In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.     

In vivo evaluation of bronchoalveolar lavage (BAL) fluid in atopic bronchial asthma, chronic bronchitis and sarcoidosis patients

The intensity of inflammatory response was evaluated in skin test on guinea pig using bronchoalveolar lavage (BAL) fluid obtained from patients with some diseases of the respiratory tract. The results of skin test were verified with activities of proteases in BAL fluid. The study was performed on 24 patients with atopic bronchial asthma, 21 with chronic bronchitis, 13 with sarcoidosis (II phase) and 18 control subjects. All patients were undergoing fiberoptic bronchoscopies and BAL fluid was obtained. The results of skin test on guinea pig using BAL fluid were correlated with the activities of acid and neutral proteases. The highest activity of proteases and intensity of skin reactions were noted in patients with atopic bronchial asthma and sarcoidosis. Authors suggest that the skin test on guinea pig with BAL fluid may be useful tool for total evaluation of inflammatory response in patients with atopic bronchial asthma, chronic bronchitis and sarcoidosis.     

Chronic bronchitis: the role of viruses

Mucus is produced by the epithelial cells in the glands, gland ducts, and the cells lining the airway lumen in the lower airways.The chronic cough and sputum production that defines chronic bronchitis is associated with an inflammatory reaction involving this mucus-secreting apparatus. Respiratory viral infections target the epithelial cells of the lung producing desquamation, microvascular dilatation, edema, and an inflammatory cell infiltrate. These changes predispose the lower airways to bacterial infection by interfering with mucociliary clearance and reducing bacterial killing by macrophages. The exact role of those infections in the pathogenesis of chronic bronchitis has not been clearly determined but they probably play a critical role in inducing bacterial colonization and initiating acute exacerbations of COPD. This article reviews the classification of the viral agents responsible for respiratory tract infection and the nature of the changes they produce in the normal airways and in the airways of patients with chronic bronchitis during acute infections.     

Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-beta-D-glucosaminidase activity in bronchoalveolar lavage fluid

High level ozone exposure is known to cause acute, neutrophil-independent airway hyperreactivity in the guinea pig. The precise biochemical mechanisms involved remain unclear. Because of its potential pathophysiologic importance, we examined whether a lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAGA) was released from the airways in vivo and from bronchoalveolar cells, specifically macrophages. Muscarinic reactivity was determined by measuring specific airway resistance (sRaw) in response to increasing doses of aerosolized acetylcholine in guinea pigs that were either exposed to air or to ozone (3.0 ppm, 2 h). The ozone-exposed animals showed substantial muscarinic hyperreactivity 30 min after exposure. In addition, both total and percent released NAGA in bronchoalveolar lavage fluid obtained immediately after reactivity testing were significantly greater in the ozone-exposed group. It was also found that substantially more NAGA was released from mixed bronchoalveolar lavage cells in response to 20 microM A23187. Moreover, bronchoalveolar macrophages of ozone-exposed animals secreted more NAGA upon stimulation in vitro by either 20 microM A23187 or 200 micrograms/ml opsonized zymosan. We conclude that ozone-induced airway hyperreactivity in guinea pigs is associated with the presence of increased NAGA activity in bronchoalveolar fluid. Our data suggest that bronchoalveolar macrophages may, at least in part, be responsible for release of this enzyme into the airways after ozone exposure.     

Evaluation of elastase and antielastase balance in patients with chronic bronchitis and pulmonary emphysema

On the basis of the "protease-antiprotease imbalance" theory for the pathogenesis of pulmonary emphysema, we hypothesized that measurement of elastase burden and antielastase capacity in the alveolar space might correlate with emphysema. To evaluate this, the severity of emphysema, the elastase burden, and the elastase inhibitory capacity were estimated in 28 patients with chronic bronchitis and variable degrees of emphysema, none of whom had congenital deficiency of alpha-1-protease inhibitor, and all of whom underwent bronchoalveolar lavage. Emphysema was assessed by both computed tomography and diffusing capacity. To examine "elastase burden," elastase:alpha-1-protease inhibitor complex and free elastase activity in alveolar lavage fluids were measured. To evaluate "antielastase" capacity, elastase inhibiting capacity in alveolar lavage fluid was measured. Elastase burden correlated directly and antielastase capacity correlated inversely with emphysema. These data provide direct support for the "protease-antiprotease imbalance" theory of emphysema in a group of smokers without congenital deficiency of alpha-1-protease inhibitor.     

Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children.

The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-h intraoesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9 +/- 3.5 (mean +/- SEM) which were higher than LLI in healthy adults (1.0 +/- 0.4), (p=0.045). Children with CF had very high LLIs (19.2 +/- 4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction.     

The role of the inflammatory response in chronic bronchitis: therapeutic implications

Chronic bronchitis is diagnosed clinically by a chronic productive cough. As implied by the term "bronchitis," chronic airway inflammation is typically found in the central airways in patients with persistent cough and mucous hypersecretion. Although the exact pathogenesis of chronic bronchitis remains unclear, bacterial colonization and the resulting inflammatory response are thought to be of central importance. The generation of pro-inflammatory cytokines and chemotactic stimuli by the airway epithelium likely play central roles in propagating the inflammatory response in patients with chronic bronchitis. Further insights into the initiating events and underlying mechanisms that result in the clinical syndrome of chronic bronchitis will likely provide novel opportunities for therapeutic interventions.